Local anesthetics are drugs that can produce a reversible loss of sensation when applied to nerve tissues. They interfere with the conduction process of the nerve tissues by blocking use-dependent voltage-gated Na+ channels and thus inhibit initiation and propagation of action potentials of the nerve tissues. At present, more than ten types of local anesthetics are in use, including, for example, bupivacaine, lidocaine, cocaine, mepivacaine, tetracaine, and ropivacaine. These drugs can be cataloged into esters and amides according to their metabolic processes, in which the former type is metabolized mainly in the blood through hydrolysis by esterases whereas the latter type is metabolized in the liver. In terms of pharmacological mechanism, these two types of local anesthetics both achieve effects of infiltrative cutaneous anesthesia, peripheral nerve blocking, and spinal/epidural anesthesia through Na+ channel blocking (McLure, et al. (2005), Minerva Anesthesiol., 71:59-74 (2005); Scholz, Br J. Anaesth., 89:52-61 (2002); Fozzard, et al., Curr. Pharm. Des., 11:2671-2686 (2005); Ruetsch, et al. (2001), Curr. Top. Med. Chem., 1:175-182 (2001).
When applied locally to a nerve tissue in appropriate concentrations, local anesthetics reversibly block the action potentials responsible for nerve conduction. Local anesthetics act on any part of the nervous system and on every type of nerve fiber. Thus, a local anesthetic in contact with a nerve trunk can cause both sensory and motor paralysis in the area enervated. Therefore, although the goal of topical or regional anesthesia is to block the transmission of signals in nociceptors to prevent pain, the administration of local anesthetics also produces numbness from block of low-threshold pressure and touch receptors, paralysis from block of motor axons, and block of autonomic fibers. A strategy for generating pain-restricted local anesthesia while preserving motor and autonomic responses is desirable in conditions such as childbirth, some dental procedure or in treating nociceptor-driven chronic pain such as postherptic neuralgia. Sensory-specific nerve block has been achieved in the prior art by using capsaicin in conjunction with the quaternary lidocaine derivative QX-314 (Clifford, et al., Nature, 449:607-610 (2007)). Thus, there is still a need for compositions that provide sensory-specific nerve block.
It is therefore an object of the invention to provide a formulation for local anesthesia that is selective for sensory blockade.
It is still another object of the invention to provide a method of local anesthesia that is selective for sensory blockade.